Mutation analysis of BRIP1/BACH1 in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives

Breast Cancer Res Treat. 2009 May;115(1):51-5. doi: 10.1007/s10549-008-0052-z. Epub 2008 May 16.

Abstract

The proper interaction between BRIP1/BACH1 and BRCA1 protein has been found to be crucial for BRCA1-mediated DNA double-strand break repair and BRIP1/BACH1 mutations were estimated to confer a relative risk for breast cancer of 2.0 in western populations. In Chinese population, BRCA1 mutations could explain a relatively large proportion of inherited breast cancer cases in comparison with BRCA2 mutations, which probably deduced a hypothesis that those genes involved in BRCA1-mediated DNA repair pathway might play a more significant role in the etiology of Chinese breast cancer. To investigate the contribution of BRIP1/BACH1 mutations to the predisposition of Chinese non-BRCA1/BRCA2 hereditary breast cancer, we screened all the coding exons and adjacent intronic splice junction regions of BRIP1/BACH1 in 357 Chinese women with early-onset breast cancer or affected relatives from five different breast disease clinical centers in China, using PCR-DHPLC and DNA sequencing analysis. Some genetic variants identified in the cases were then studied in 864 normal controls with no personal or family history of breast cancer. We found no protein-truncated mutations in our population, while a novel recurrent non-synonymous variant, Q944E, was detected in two independent families in contrast with none in the controls, interestingly, this alteration occurs in the BRCA1 binding domain of the BACH1 protein. Then a further study performed on the two mutation positive families revealed the partial co-segregation of this mutation allele with cancer. The novel alteration Q944E identified in our study possibly represents a rare disease-related allele, nevertheless functional analysis is still warranted to resolve the ability of this altered BACH1 protein to bind BRCA1. Altogether, the results of our study indicated that germline mutations in BRIP1/BACH were extremely rare in Chinese population and there was no evidence for the recommendation of BRIP1/BACH1 for genetic testing in Chinese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Breast Neoplasms / genetics*
  • China
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Exons
  • Family Health
  • Fanconi Anemia Complementation Group Proteins / genetics*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • RNA Helicases / genetics*

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group Proteins
  • BRIP1 protein, human
  • RNA Helicases